经皮寰枢椎螺钉内固定手术的并发症分析

目的：总结经皮寰枢椎螺钉内固定手术的并发症发生情况。方法：2001年3月～2006年5月在我科行经皮寰枢椎螺钉内固定手术并获得至少18个月随访的患者87例，其中经皮前路齿状突螺钉内固定手术者43例，经皮前路寰枢椎关节螺钉内固定手术者36例，经皮后路寰枢椎关节螺钉内固定手术者8例，统计并发症类型及发生率。结果：87例患者共出现并发症20例次。（1）螺钉相关并发症17例（19．5％），其中螺钉钉尾留置过长8例，均未出现临床症状，未处理；螺钉误置6例，其中1例行螺钉调整，1例拔除螺钉，另4例无症状者未处理；骨折端再移位2例，1例改行后路融合手术，另1例轻度移位者经支具固定3个月后骨折愈合：1例术后3个月发现螺钉松动脱出但无症状，术后1年寰枢关节融合后拔除螺钉；再手术者共4例（4．6％）：（2）螺钉不相关并发症共3例，其中穿刺并发症1例，患者术后第3天出现喉上神经麻痹，经营养神经药物治疗5周后恢复正常；切口表浅感染1例，肺部感染1例，均经抗感染治疗后好转。无其他重要神经和血管损伤。结论：经皮寰枢椎螺钉内固定手术并发症多数较轻微，无需特殊处理，严重及需再手术的并发症比率低。     

成人新鲜Ⅱ型、浅Ⅲ型齿状突骨折手术治疗效果分析

目的 :探讨颈前路齿状突螺钉内固定术和颈后路寰枢椎椎弓根螺钉内固定植骨融合术治疗成人新鲜Ⅱ型、浅Ⅲ型齿状突骨折的临床疗效。方法:回顾分析我院2010年3月~2016年3月手术治疗的成人新鲜齿状突骨折23例,根据Anderson-D′Alonzo分型,Ⅱ型17例,浅Ⅲ型6例,男15例,女8例,年龄15~68岁(41.2±15.1岁)。患者入院时均有颈部疼痛、颈部活动受限;其中5例有不同程度脊髓神经损伤表现,术前JOA评分10~14分(12.8±1.6分)。13例齿状突骨折无移位或牵引后复位良好的Ⅱa型、Ⅱb型、浅Ⅲ型患者行颈前路齿状突螺钉内固定术,8例牵引后复位不理想及2例Ⅱc型齿状突骨折患者行颈后路寰枢椎椎弓根螺钉内固定植骨融合术。结果:术后23例患者均未出现血管、食道损伤及脊髓神经损伤加重等并发症。术后23例患者随访8~30个月(18.0±6.4个月)。5例合并脊髓损伤患者术后半年JOA评分14~17分(16.3±1.3分),平均改善率为83.3%。术后影像学复查寰枢椎对应关系良好,内固定无松动、断裂。术后1例前路齿状突螺钉内固定患者随访至8个月时骨折端尚未愈合,其余12例齿状突螺钉内固定均骨性愈合。10例寰枢椎椎弓根螺钉内固定植骨患者植骨均获得骨性融合。结论:颈前路齿状突螺钉内固定和颈后路寰枢椎椎弓根螺钉内固定植骨融合术治疗成人新鲜Ⅱ型、浅Ⅲ型齿状突骨折,固定牢固,愈合率高,具有良好的临床疗效。     

齿状突骨折经皮前路螺钉内固定术的适应证与疗效分析

[目的]探讨齿状骨折经皮前路螺钉内固定术的适应证和临床疗效.[方法]齿状突骨折19例,Ⅱ型骨折16例,Ⅲ型骨折3例.伴寰椎前脱位10例,后脱位4例,无移位5例.有寰枢椎脱位者术前先行颅骨牵引复位,X线片显示复位满意后,行经皮前路螺钉内固定术.[结果]19例患者术中、术后X线片显示齿状突骨折复位满意、稳定.术后平均随访18.5个月,骨性愈合15例,不愈合2例,延迟愈合2例.[结论]经皮前路螺钉内固定治疗齿状突骨折具有微创、内固定牢靠、早期活动等优点,适应证选择是临床疗效的关键.     

Ⅱ型齿状突骨折的手术治疗

目的 探讨Ⅱ型齿状突骨折行手术治疗的疗效.方法 对12例Ⅱ型齿状突骨折分别采用前路空心螺钉内固定术和寰枢椎椎弓根钉内固定术.结果 本组获3～24个月的随访,内固定均无松动,骨折均愈合和植骨融合.结论 前路空心螺钉内固定术适合治疗齿状突骨折ⅡB型,寰枢椎椎弓根钉适合ⅡC型.     

经皮前路空心钉内固定治疗新鲜Ⅱ型齿状突骨折

目的 评价经皮前路空心钉内固定治疗新鲜Ⅱ型齿状突骨折的临床疗效。方法 自2009-05-2013-02采用经皮前路空心钉内固定治疗新鲜Ⅱ型齿状突骨折15例,根据Anderson-D＇Alonzo分型方法,均为Ⅱ型。记录手术时间、术中出血量、住院时间及并发症情况,术后摄X线片观察寰枢椎稳定和内固定物位置情况。结果 手术时间84-125 min,平均98.7 min;术中出血量8-30 ml,平均11.2 ml。15例均获得良好复位,切口均一期愈合。本组获得随访10-21个月,平均13.8个月。X线片显示骨折均愈合,螺钉位置良好,寰枢椎稳定。骨折愈合时间4-9个月,平均6.8个月;无血管、神经、气管及内固定物失效等并发症。结论 采用经皮前路空心钉内固定治疗新鲜Ⅱ型齿状突骨折,具有创伤小、恢复快及骨折足够稳定性等特点,是治疗Ⅱ型齿状突骨折较为理想的方法,但应严格掌握手术适应证。     

上颈椎不稳前路内固定方式的选择

目的:探讨上颈椎不稳前路内固定手术方式的选择及治疗效果。方法:自2000年3月至2010年9月,采用寰枢椎前路内固定手术治疗上颈椎不稳83例,男59例,女24例;年龄20～68岁,平均42岁。其中齿状突螺钉内固定36例,寰枢椎前路经关节螺钉内固定16例,C2,3前路钢板内固定23例,齿状突螺钉联合寰枢椎经关节螺钉内固定5例,齿状突螺钉联合C2,3钢板内固定2例,寰枢椎经关节螺钉联合C2,3钢板内固定1例。结果:1例颈脊髓完全损伤患者,行寰枢椎经关节螺钉内固定,术后1个月死于肺部感染。其余病例获得随访,时间8个月～3年,平均15个月。无椎动脉及脊髓损伤,所有病例寰枢椎获得稳定。36例齿状突螺钉内固定及5例齿状突联合寰枢椎经关节螺钉内固定者,未植骨,齿状突骨性愈合。寰枢椎经关节螺钉内固定病例:1例并发肺部感染死亡;1例齿状突ⅡC型粉碎性骨折并寰枢关节前脱位,齿状突及植骨未骨性愈合,但寰枢关节纤维连接无不稳定表现;1例寰枢椎陈旧性前脱位Ⅰ期前路寰枢椎经关节螺钉内固定,Ⅱ期后路Brooks钢丝内固定后路植骨,寰枢椎骨性融合。其他病例均植骨并获骨性融合。结论:上颈椎不稳患者,根据不同的骨折及不稳类型,选择相应的前路内固定,可取得较好疗效。     

创伤性寰枢椎不稳的手术治疗策略

目的探讨创伤性寰枢椎不稳的手术治疗方式,指导选择安全稳定可靠的术式。方法29例创伤性寰枢椎不稳的病例,男22例,女7例;年龄16~52岁,平均32岁。齿状突骨折19例中,Ander-sonⅡ型16例,浅Ⅲ型3例;另外,寰椎横韧带损伤6例,陈旧性寰枢关节旋转性脱位1例,HangmanⅠ型骨折合并齿状突骨折1例,寰椎骨折合并寰椎横韧带损伤1例,齿状突骨折合并单侧枢椎上关节骨折1例。根据不同的损伤部位选择相应的手术方法,其中前路单枚齿状突螺钉固定10例,后路Magerl螺钉固定6例,Magerl联合Gallie5例,Magerl联合Brooks双钛缆固定2例,Magerl联合Apofix椎板夹固定2例,寰枢椎侧块钉板固定4例。19例后路手术中11例采用C1、C2椎板间颗粒状植骨,8例未行植骨融合。结果随访时间6个月~5年,平均18个月。术中未出现椎动脉或脊髓损伤等严重并发症,无内固定断裂。1例术后出现舌下神经麻痹,2周后缓解。10例前路齿状突螺钉固定中9例获得骨性愈合,1例齿状突螺钉固定发生松动,枢椎前方皮质破裂,取出齿状突螺钉,改行后路Magerl Gallie法固定,获得骨性融合。19例后路手术中8例未做融合的病例获骨折愈合,其中6例行内固定取出,基本恢复头颈旋转功能,其余11例均获得骨性融合。结论新鲜齿状突骨折不适于前路齿状突螺钉固定时,后路C1、C2椎弓根钉板暂时固定,可保留寰枢旋转功能。寰枢椎椎弓根钉板系统在生物力学稳定及适应证方面有一定的优势。     

前路三钉内固定治疗寰椎-齿状突Ⅱ型骨折

背景：齿状突加寰枢椎前路经关节螺钉内固定是近来治疗寰椎-齿状突Ⅱ型骨折的一种新方法,临床报道较少。 目的：探讨颈前路三钉,即齿状突螺钉加寰枢椎前路经关节螺钉内固定治疗寰椎-齿状突Ⅱ型骨折的方法及疗效。 方法：2008年2月至2011年10月于C型臂X线机透视下行颈前路齿状突螺钉加寰枢椎经关节螺钉内固定治疗寰椎-齿状突Ⅱ型骨折5例。 结果：5例骨折患者共植入5枚齿状突螺钉,9枚经寰枢关节螺钉,1例因左侧经寰枢关节螺钉进钉点处骨折而行右侧单侧固定。全部获得随访,随访时间为10~30个月,平均18个月,螺钉位置满意,齿状突骨折均获骨性愈合,寰枢关节稳定,无一例发生螺钉松动、断钉,无一例发生脊髓、椎动脉损伤等并发症。 结论：颈前路齿状突螺钉加寰枢椎经关节螺钉内固定治疗寰椎-齿状突Ⅱ型骨折,对齿状突直接固定同时即刻稳定寰枢椎,为寰椎-齿状突Ⅱ型骨折患者提供了一种新的治疗方法。     

寰枢椎内固定对陈旧齿状突骨折的作用

目的:观察陈旧齿状突骨折患者在后路寰枢椎坚强内固定融合术后骨折端的变化,探索采用寰枢椎非融合内固定治疗齿状突骨折、尤其是新鲜骨折的可行性。方法:对我院2001年2月~2012年8月采取后路寰枢椎固定融合术治疗的82例陈旧性齿状突骨折患者手术前后的影像资料进行回顾性分析。其中2005年1月~2012年8月42例有完整的术前、术后CT资料可供分析骨折端变化的患者作为研究对象,伤后手术时间3~8周5例、8周以上~36周30例、36周以上7例,40例选择经寰椎侧块-枢椎椎弓根内固定、寰椎后弓枢椎椎板间植骨融合术,2例选择经寰枢侧块关节螺钉固定融合术,术后随访时间截至寰枢间植骨融合为止。结果:所有患者寰枢椎间后方植骨发生融合,其中30例齿状突骨折也发生愈合,4例疑似愈合,8例未愈合。齿状突骨折端愈合时间:28例发生于术后4个月,1例发生于术后6个月,1例发生于术后9个月。结论:对陈旧齿状突骨折患者经后路寰枢椎间内固定可为齿状突骨折愈合提供可靠的稳定性,为采用非融合寰枢椎内固定治疗齿状突骨折尤其是新鲜骨折提供了可靠的临床依据。     

齿状突骨折合并寰枢椎不稳术式的选择及疗效观察

目的 探讨齿状突骨折合并寰枢椎不稳的手术方式选择及疗效. 方法 对2002年1月至2011年12月收治的54例齿状突骨折合并寰枢椎不稳患者的临床资料进行回顾性分析,男39例,女15例;年龄18 ～55岁,平均36岁;陈旧性齿状突骨折5例,新鲜齿状突骨折49例;齿状突骨折按Anderson-D'Alonzon分型:Ⅱ型30例,Ⅲ型24例;合并寰椎前脱位12例,寰椎后脱位12例,无明显脱位30例;术前神经功能按美国脊髓损伤协会(ASIA)分级:B级2例,C级5例,D级16例,E级31例.其中30例患者行前路齿状突空心螺钉内固定术(A组),8例患者行前路经寰枢关节螺钉内固定术(B组),16例患者行后路寰枢椎椎弓根螺钉内固定术(C组). 结果 术中无椎动脉、脊髓损伤发生,术后寰椎脱位患者均获得良好复位.所有患者术后获6～24个月(平均16个月)随访.A组2例患者术后6个月复查示骨折不愈合,A组其他患者和B、C组所有患者均在术后3～4个月骨折愈合.无螺钉松动、断钉、退钉发生.所有患者术后6个月神经功能按ASIA分级:C级2例,D级6例,E级46例. 结论 上述三种手术方式均是治疗齿状突骨折合并寰枢椎不稳的有效方法.临床根据患者具体病情首选前路齿状突空心螺钉内固定治疗,此方法不合适时可考虑行前路经寰枢关节螺钉内固定术或后路寰枢椎椎弓根螺钉内固定术等寰枢椎融合术.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.